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That magic moment when silence turns into surrender.
It is almost tragicomic: Hans-Joachim Kremer remains in total silence for nearly ten seconds as the reality of cell biology and physicochemistry threatens his dogmatic worldview – only to reject both once more like a defiant and infantile child.
It becomes particularly revealing when he calls me a "troll" while simultaneously demonstrating that he hasn't grasped even the basics of mitochondrial vulnerability. Anyone who fails to understand the link between pre-existing mitochondrial stress and LNP-triggered cardiotoxicity has no business leading debates on pathophysiology.
The absolute low point of the talk, however, was his hesitation regarding the most fundamental principle: "Let’s assume the LNPs are taken up by the cell..."
Zheng L, Bandara SR, Tan Z, Leal C. Lipid nanoparticle topology regulates endosomal escape and delivery of RNA to the cytoplasm. Proc Natl Acad Sci U S A. 2023 Jul 5;120(27):e2301067120. doi:10.1073/pnas.2301067120
Omo-Lamai S, Wang Y, Patel MN, Milosavljevic A, Zuschlag D, Poddar S, Wu J, Wang L, Dong F, Espy C, Majumder A, Essien EO, Shen M, Channer B, Papp TE, Tobin M, Maheshwari R, Jeong S, Patel S, et al. Limiting endosomal damage sensing reduces inflammation triggered by lipid nanoparticle endosomal escape. Nat Nanotechnol. 2025 Sep;20(9):1285-1297. doi:10.1038/s41565-025-01974-5
Zhao Y, Qu Z, Paloncyova M, Wang Z, Weng B, Zhao Y, et al. Spatial Conformation of Ionizable Lipids Regulates Endosomal Membrane Disruption. J Am Chem Soc. 2025 Oct 22;147(42):38265-74. doi:10.1021/jacs.5c10908
Lin X, Xiang H, Wu J, Liao R, Li Y, Xu B, Xu Y, Shen Y, Li Q, Tian Y. The evolution of lipid nanoparticles: Paving the way for next-generation nucleic acid medicines. Asian J Pharm Sci. 2026 Feb;21(1):101121. doi:10.1016/j.ajps.2026.101121
"Let’s assume"? Seriously, HaJo? How on earth is the modRNA supposed to be translated without this process? Anyone who degrades this mechanism to a mere "assumption" has failed to understand the very principle of this technology.
And while you mentally check out at terms like "endosomal disruption": The Endoplasmic Reticulum (ER) is not an optional accessory. It is the heart of the cellular machinery.
But feel free to stick to your mantra: "modRNA, modRNA, Spike, Spike, Spike." Thinking, after all, is more exhausting than reciting. Anyone who ignores the fascinating complexity of intracellular networks just to save their narrative has long since abandoned the ground of science.
Scott ZC, Koning K, Vanderwerp M, Cohen L, Westrate LM, Koslover EF. Endoplasmic reticulum network heterogeneity guides diffusive transport and kinetics. Biophys J. 2023;122(15):3191-3205. doi:10.1016/j.bpj.2023.06.022
Griffing LR. Networking in the endoplasmic reticulum. Biochem Soc Trans. 2010;38(3):747-753. doi:10.1042/BST0380747
Stefan CJ. Endoplasmic reticulum-plasma membrane contacts: Principals of phosphoinositide and calcium signaling. Curr Opin Cell Biol. 2020;63:125-134. doi:10.1016/j.ceb.2020.01.010
Li C, Qian T, He R, Wan C, Liu Y and Yu H (2021) Endoplasmic Reticulum–Plasma Membrane Contact Sites: Regulators, Mechanisms, and Physiological Functions. Front. Cell Dev. Biol. 9:627700. doi: 10.3389/fcell.2021.627700
Raiborg C, Wenzel EM, Stenmark H. ER-endosome contact sites: molecular compositions and functions. EMBO J. 2015 Jul 14;34(14):1848-58. doi:10.15252/embj.201591481. Epub 2015 Jun 3. PMID: 26041457; PMCID: PMC4547891
Wenjing Li et al. Endoplasmic reticulum junctions serve as a platform for endosome-lysosome interactions through their stop-and-go motion switching.Sci. Adv.11,eadv4437(2025).doi:10.1126/sciadv.adv4437
Hamsanathan S and Gurkar AU (2022) Lipids as Regulators of Cellular Senescence. Front. Physiol. 13:796850. doi: 10.3389/fphys.2022.796850
Zeng Q, Gong Y, Zhu N, Shi Y, Zhang C, Qin L. Lipids and lipid metabolism in cellular senescence: Emerging targets for age-related diseases. Ageing Res Rev. 2024;97:102294. doi:10.1016/j.arr.2024.102294
And the most striking part: He does not understand a single word of the quoted papers and comes with the most stupid excuses like following screenshot:
Our HaJo is arguing at the level of a mechanic trying to repair a quantum computer with a hammer. And the best part: he clearly tuned out during the entire two-hour talk, presumably too busy listening to the sound of his own voice.
There is no other way to explain his tertiary amine argument; equating a free molecule with a molecular assembly is like comparing apples to asteroids: just because they both occupy space doesn't mean they follow the same laws of physics. His Onpattro comparison is equally flawed. Furthermore, he obviously hasn't even grasped the contradictions within the official FDA regulatory data.
Well, it’s easy when you can just cherry-pick your arguments: "Lab findings vs. Real-World Data." But here’s the kicker: If Real-World Data itself relies entirely on lab findings–which is mandatory for detecting modRNA or Spike protein in the first place–then by his own logic, HaJo shouldn't believe in the modRNA theory either. So, which is it? Oh, I see: it’s the classic "I win, you lose" playground logic, shifting the goalposts whenever it suits his narrative.
Read the papers listed here, or don't. But stop faking clinical expertise where you haven't even grasped the basics of intracellular membrane dynamics.
Nano physics and physicochemistry do not wait for your understanding.
#curvature; #lipidpackaging, #lipophilicorganisation, #kineticminimum, #vromaneffect, #softphysics matters.
P.s.: And while you continue to obsess over the half-life of single, non-protonated molecules, the scientific community has already moved on to confirming mitochondrial damage and induced senescence in vitro and even more in vivo for BNT162b2:
Van Praet JT, De Groote M, De Bacquer D, Verhalleman E, Welvaert Z, Emmerechts J, Reynders M, De Vriese AS. Immune Senescence Markers Predict the Cellular Immune Response to BNT162b2 Vaccination in Hemodialysis Patients. Open Forum Infect Dis. 2022 Oct 31;9(11):ofac585. doi:10.1093/ofid/ofac585. PMID: 36408467; PMCID: PMC9669454
Lee H, Häffner M, Balog S, Taladriz-Blanco P, Mroczek A, Staudinger S, Petri-Fink A, Rothen-Rutishauser B. Long-term exposure to nanoparticles alters senescence-associated markers and immune responses in human monocyte-derived macrophages. Nanoscale. 2026 Mar 18;18(10):5517-5530. doi:10.1039/d5nr05035a. PMID: 41677161; PMCID: PMC12896121
Wang, Kun, ZhiqiangWang, TongZhang, et al. 2026. “Lipid Nanoparticles Delivering ClpP-mRNA Suppress Pyroptosis and Senescence in Intervertebral Disc Degeneration via mTOR/BNIP3-Activated Mitophagy,” Rare Metals: e70060 doi:10.1002/rar2.70060. (tricky paper: Guess what’s missing as driver of senescence and the breakdown >96hours…The mouse data?: “fixed with 4% paraformaldehyde, decalcified, and sealed with wax, followed by HE staining and IHC staining” this was a good one.)
